We plan to continue studies of the nitrogen metabolism of nervous tissue directed to specific problems related to the effects of naturally occurring amino acids and related substances on neuronal excitability and synaptic transmission as well as to their roles in general metabolism and maintenance in nervous tissue in health and disease. This project is concerned with the role of the gamma-aminobutyric acid (GABA) system in the central nervous system function. We are attempting to obtain answers in some of the following areas as suitable tools become available: (a) formation and metabolism of GABA in the nervous system; properties and control mechanisms of the glutamic decarboxylase and GABA transaminase systems, (b) evidence for the presynaptic release of GABA, (c) mechanism of action of GABA on membranes, (d) consideration of the transport into intracellular sites as the major mode of the removal of GABA from the synaptic cleft, (e) study of antagonists of the depressant action of GABA and the membrane changes produced by it, (f) role of the GABA system in cerebellum, (g) the role of GABA in the retina and other vertebrate neuronal systems. A plan is being made to test the idea that there may be primary defect in the GABA system in individuals with a susceptibility to schizophrenia. Glutamic acid decarboxylase (GAD), the enzyme in brain that forms GABA, was visualized on sections of rat cerebellum employing rabbit antiserum to purified mouse brain GAD. Cerebellar sections obtained from rats that were perfused with 4% paraformaldehyde were treated with anti-GAD serum or with serum from unimmunized rabbits, washed, and then incubated with peroxidase-labeled goat antibody against rabbit immunoglobulin. The GAD was visualized on sections by means of the product formed by the action of peroxidase on 3,3'-diaminobenzidine and H2O2. A weak and diffuse reaction was observed in Purkinje cell bodies suggesting the occurrence of GAD within these cells. In addition, an intense punctate deposition of reaction product was located around the Purkinje cells and around the neurons of the deep cerebellar nuclei suggesting the impingement of many nerve terminals containing GAD upon these neuronal surfaces. No specific reaction product was observed on sections when serum from unimmunized rabbits was used. (Text Truncated - Exceeds Capacity)